LIMCH1 is Downregulated and Associated With Poor Prognosis, and Suppresses Tumor Cell Proliferation and Invasion in Ovarian Cancer

Background: LIM and calponin homology domain-containing protein 1 (LIMCH1) regulates myosin stress fiber assembly and cell motility and is involved in carcinogenesis. However, its role in ovarian cancer remains poorly characterized. In this study, LIMCH1 was identified as a candidate tumor suppressor gene through analysis of Gene Expression Omnibus (GEO) datasets, and its clinical relevance and regulatory function in ovarian cancer were investigated. Methods: The GSE102094, GSE160626, and GSE190688 datasets were used to identify differentially expressed genes (DEGs) between ovarian cancer tissues and control tissues, whereas the GSE102094 and GSE160626 datasets were used to identify DEGs between platinum-resistant and platinum-sensitive ovarian cancer tissues. Gene Expression Profiling Interactive Analysis (GEPIA) was used to evaluate the clinical relevance of LIMCH1 in ovarian cancer, and the findings were further validated by immunohistochemical analysis of 70 ovarian cancer tissues and 10 control tissues. Functional validation of LIMCH1 was performed by transfecting SKOV3 and CAOV-3 cells with LIMCH1 overexpression plasmids or LIMCH1-specific siRNA. A xenograft model was established by injecting SKOV3 cells transduced with either LIMCH1-overexpressing lentivirus or NC lentivirus. Results: A total of 177 DEGs were identified by intersecting ovarian cancer-associated DEGs with platinum resistance-associated DEGs, which were mainly enriched in pathways related to cell cycle regulation, cell junctions, and carcinogenesis. Among these candidates, LIMCH1 was selected for further exploration. Analysis of the GEPIA database demonstrated that LIMCH1 expression was significantly reduced in ovarian cancer tissues, and markedly low LIMCH1 expression was associated with poor overall survival in patients with ovarian cancer. Immunohistochemical analysis further confirmed the downregulation of LIMCH1 expression in ovarian cancer tissues. Moreover, LIMCH1 expression showed good diagnostic performance for distinguishing ovarian cancer from the control tissues, with an area under the receiver operating characteristic curve (AUC) of 0.794. Furthermore, LIMCH1 expression was negatively correlated with tumor stage and pathological grade. In vitro experiments discovered that LIMCH1 suppressed SKOV3 and CAOV-3 cell proliferation and invasion, while promoting apoptosis and increasing carboplatin sensitivity. In vivo experiments further showed that LIMCH1 inhibited tumor progression. Conclusions: These findings suggest that LIMCH1 may function as a novel tumor suppressor involved in the pathogenesis of ovarian cancer.